Mohamed Faiezah A A, Roberts Matthew, Seton Linda, Ford James L, Levina Marina, Rajabi-Siahboomi Ali R
School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University , Liverpool , UK and.
Drug Dev Ind Pharm. 2015 Jan;41(1):70-8. doi: 10.3109/03639045.2013.845843. Epub 2013 Oct 17.
The particle size of HPMC is a critical factor that can influence drug release rate from hydrophilic matrix systems. Percolation theory is a statistical tool which is used to study the disorder of particles in a lattice of a sample. The percolation threshold is the point at which a component is dominant in a cluster resulting in significant changes in drug release rates. Mini-tablets are compact dosage forms of 1.5-4 mm diameter, which have potential benefits in the delivery of drug to some patient groups such as pediatrics. In this study, the effect of HPMC particle size on hydrocortisone release and its associated percolation threshold for mini-tablets and tablets was assessed. For both mini-tablets and tablets, large polymer particles reduced tensile strength, but increased the drug release rate and the percolation threshold. Upon hydration, compacts with 45-125 μm HPMC particles formed a strong gel layer with low porosity, reducing hydrocortisone release rates. In comparison, faster drug release rates were obtained when 125-355 µm HPMC particles were used, due to the greater pore sizes that resulted in the formation of a weaker gel. Using 125-355 µm HPMC particles increased the percolation threshold for tablets and to a greater extent for mini-tablets. This work has demonstrated the importance of HPMC particle size in ER matrices, the effects of which are even more obvious for mini-tablets.
羟丙基甲基纤维素（HPMC）的粒径是影响亲水性基质系统中药物释放速率的关键因素。渗流理论是一种统计工具，用于研究样品晶格中颗粒的无序状态。渗流阈值是指某一组分在聚集体中占主导地位，从而导致药物释放速率发生显著变化的点。微型片是直径为1.5 - 4毫米的紧凑型剂型，在向儿科等一些患者群体给药方面具有潜在优势。在本研究中，评估了HPMC粒径对微型片和普通片中氢化可的松释放的影响及其相关的渗流阈值。对于微型片和普通片而言，较大的聚合物颗粒会降低拉伸强度，但会提高药物释放速率和渗流阈值。水化后，含有45 - 125μm HPMC颗粒的压片形成了低孔隙率的强凝胶层，降低了氢化可的松的释放速率。相比之下，使用125 - 355μm HPMC颗粒时，由于较大的孔径导致形成较弱的凝胶，药物释放速率更快。使用125 - 355μm HPMC颗粒提高了普通片的渗流阈值，对微型片的影响更大。这项工作证明了HPMC粒径在缓释基质中的重要性，其对微型片的影响更为明显。
